The ubiquitin-like protein PLIC-1 or ubiquilin 1 inhibits TLR3-Trif signaling

Autor: Tianyi Wang, Weiqun Liu, Tapani Ronni, Shufeng Liu, Nabanita Biswas, Steven E. Aussenberg, Takashi Fujita
Rok vydání: 2010
Předmět:
Autophagosome
lcsh:Medicine
Autophagy-Related Proteins
Cell Cycle Proteins
Biochemistry
Small hairpin RNA
0302 clinical medicine
Genes
Reporter
Molecular Cell Biology
Signaling in Cellular Processes
RNA
Small Interfering
lcsh:Science
Luciferases
Promoter Regions
Genetic
0303 health sciences
Multidisciplinary
NF-kappa B
MDA5
Innate Immunity
3. Good health
RNA silencing
Protein Transport
Gene Knockdown Techniques
Signal transduction
Transmembrane Signaling
Signal Transduction
Research Article
Immunology
Newcastle disease virus
Down-Regulation
Biology
03 medical and health sciences
Cell Line
Tumor
Two-Hybrid System Techniques
Humans
030304 developmental biology
Adaptor Proteins
Signal Transducing
Inflammation
lcsh:R
Immunity
RNA
Proteins
Immunoregulation
Interferon-beta
Molecular biology
Toll-Like Receptor 3
Transmembrane Proteins
Adaptor Proteins
Vesicular Transport
HEK293 Cells
Poly I-C
TRIF
TLR3
lcsh:Q
Carrier Proteins
030217 neurology & neurosurgery
Zdroj: PLoS ONE
PLoS ONE, Vol 6, Iss 6, p e21153 (2011)
ISSN: 1932-6203
Popis: Background: The innate immune responses to virus infection are initiated by either Toll-like receptors (TLR3/7/8/9) or cytoplasmic double-stranded RNA (dsRNA)-recognizing RNA helicases RIG-I and MDA5. To avoid causing injury to the host, these signaling pathways must be switched off in time by negative regulators. Methodology/Principal Findings: Through yeast-two hybrid screening, we found that an ubiquitin-like protein named protein linking integrin-associated protein to cytoskeleton 1(PLIC-1 or Ubiquilin 1) interacted with the Toll/interleukin-1 receptor (TIR) domain of TLR4. Interestingly, PLIC-1 had modest effect on TLR4-mediated signaling, but strongly suppressed the transcriptional activation of IFN-β promoter through the TLR3-Trif-dependent pathway. Concomitantly, reduction of endogenous PLIC-1 by short-hairpin interfering RNA (shRNA) enhanced TLR3 activation both in luciferase reporter assays as well as in new castle disease virus (NDV) infected cells. An interaction between PLIC-1 and Trif was confirmed in co-immunoprecipitation (Co-IP) and GST-pull-down assays. Subsequent confocal microscopic analysis revealed that PLIC-1 and Trif colocalized with the autophagosome marker LC3 in punctate subcellular structures. Finally, overexpression of PLIC-1 decreased Trif protein abundance in a Nocodazole-sensitive manner. Conclusions: Our results suggest that PLIC-1 is a novel inhibitor of the TLR3-Trif antiviral pathway by reducing the abundance of Trif. © 2011 Biswas et al.
Databáze: OpenAIRE
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